Use of gastrointestinal prokinetics and the risk of parkinsonism: A population-based case-crossover study

The disease burden of parkinsonism is extremely costly in the United States. Unlike Parkinson's disease, drug-induced parkinsonism (DIP) is acute and reversible; exploring the causative drug is important to prevent DIP in patients at high-risk of parkinsonism. To examine whether the use of gastrointestinal (GI) prokinetics is associated with an increased risk of parkinsonism. We conducted a case-crossover study using nationally representative data. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) between January 1, 2007 and December 1, 2015. The first prescription date of G20, G21.1, or G25.1 diagnoses was defined as the index date (0 day). Patients with prior extrapyramidal and movement disorders or brain tumors were excluded. We assessed the exposure within the risk (0-29 days) and control periods (60-89 days), before or on the index date. Conditional logistic regression estimated the adjusted odds ratio (aOR) for parkinsonism. Overall, 2268 and 1674 patients were exposed to GI prokinetics during the risk and control periods, respectively. The use of GI prokinetics significantly increased the occurrence of parkinsonism (aOR = 2.31; 95% Confidence Interval [CI], 2.06-2.59). The use of GI prokinetics was associated with a higher occurrence of parkinsonism in elderly patients (≥65 years old; aOR = 2.69; 95% CI, 2.30-3.14) than in younger patients (aOR = 1.90; 95% CI, 1.59-2.27). The use of GI prokinetics was significantly associated with higher occurrences of parkinsonism, necessitating close consideration when using GI prokinetics.